Prevention and treatment of allergic inflammation by an Fcγ-Der f2 fusion protein in a murine model of dust mite-induced asthma

被引:12
作者
Lin, Li-hui [1 ]
Zheng, Ping [2 ]
Yuen, John W. M. [3 ]
Wang, Juan [1 ]
Zhou, Juan [1 ]
Kong, Cun-quan [1 ]
Peng, Xia [1 ]
Li, Jia [1 ]
Li, Li [1 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 1, Dept Lab Med, Shanghai 200080, Peoples R China
[2] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 1, Dept Gastroenterol, Shanghai 200080, Peoples R China
[3] Hong Kong Polytech Univ, Sch Nursing, Hong Kong, Hong Kong, Peoples R China
关键词
Fc epsilon RI; Fc gamma RIIb; Fc gamma-Der f2 fusion protein; Immunomodulation; Allergic asthma mouse; NECROSIS-FACTOR-ALPHA; MAST-CELL ACTIVATION; T-CELLS; RECEPTORS; IGE; ANAPHYLAXIS; INHIBITION; EXPRESSION; RESPONSES; AFFINITY;
D O I
10.1007/s12026-012-8339-x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The immunoglobulin E (IgE) high-affinity receptor Fc epsilon RI expressed on mast cells and basophils plays a critical role in triggering allergic disease. The co-aggregation of the Fc epsilon RI and Fc gamma RIIb receptors is inhibitory to Fc epsilon RI signaling and holds great potential for the treatment of IgE-mediated allergies. In China, is a common anaphylaxis trigger. Therefore, in this study, the Fc gamma RIIb-mediated immunomodulating activity of recombinant Fc gamma-Der f2 fusion protein was tested in a Der f2-allergic murine model. Following the treatment, bronchoalveolar lavage fluid (BALF) was collected to measure the expression of several Th1/Th2-type cytokines (IL-5, TNF-alpha, IL-12p70, IL-4, IL-10, IFN-gamma and IL-18) and histamine, while blood was used to detect the specific IgE and IgG-types anti-Der f2 antibodies, for measurement. In contrast to the saline-treated allergic mice, the levels of Der f2-specific IgE, cytokines and histamine were lowered in the Fc gamma-Der f2-treated allergic mice, in addition to the rare inflammatory cell infiltration in the airways and blood vessels revealed by histopathological examination. The recombinant Fc gamma-Der f2 protein was demonstrated to function as an effective immunotherapeutic agent, suggesting that chimeric human Fc gamma-allergen proteins could be used in the development of antigen-specific immunotherapy for human allergic diseases.
引用
收藏
页码:276 / 283
页数:8
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